A viral etiology has been proposed for the chronic inflammatory bowel disease, Crohn's disease or regional enteritis. Recent studies have reported the isolation of a fastidious viral agent, antigenically related to the Nebraska calf diarrhea rotavirus. This proposal seeks to examine the disease-virus association through the use of sensitive immunocytochemical (peroxidase-antiperoxidase complexes) and biochemical (nucleic acid hybridization) tests. The simian rotavirus SA11 has been selected as a model probe because it is a more effective antigen for the detection of human rotavirus infections than the Nebraska calf diarrhea virus. In addition, in contrast to the fastidious agent recovered from human tissue, SA11 can be grown to high titers in culture, an attribute important for the preparation of radiolabeled nucleic acid for hybridization studies and for the preparation of hyperimmune sera for immunocytochemical tests. These complementary, sensitive molecular techniques will be used to determine the prevalence and distribution of viral antigens and genetic information in bowel tissues from patients with Crohn's disease or ulcerative colitis as compared to normal tissue obtained from patients undergoing resection associated with intestinal bypass surgery or trauma. In addition, the relationship between human viral isolates and the granulomatous disease induced in animal models will be determined. The results of this study would be of great benefit to our understanding of the nature of the disease, the development of an authentic animal model, and development of a rational therapeutic approach to individuals suffering from Crohn's disease.